Cited by 202Ethics in Clinical ResearchStatistical Methods in Clinical TrialsBiomedical Ethics and Regulation

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Ethical issues in stopping randomized trials early because of apparent benefit.

Mueller, Paul S., Montori, Victor M., Bassler, Dirk, Koenig, Barbara A., Guyatt, Gordon H.·2007·Annals of Internal Medicine

DOI 10.7326/0003-4819-146-12-200706190-00009

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Abstract

Stopping randomized trials early because of an apparent benefit is becoming more common. To protect and promote the interests of trial participants, investigators may feel obligated to stop a trial early because of the apparent benefit of a study treatment (compared with placebo or other treatment). There are, however, serious ethical problems with doing so. Truncated trials systematically overestimate treatment effects; in cases where the number of accrued outcome events is small, the overestimation may be very large. Generating seriously inflated estimates of treatment effect violates the ethical research requirement of scientific validity. Subsequent use of inflated estimates to inform clinical decision making and practice guidelines violates the ethical requirements of social value and a favorable risk-benefit ratio. Researchers should ensure that a large number of outcome events accrues before stopping a trial and then continue recruitment to assess whether positive trends continue. This can balance the need to protect research participants with the ethical requirements of scientific validity, social value, and a favorable risk-benefit ratio.

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Authors: Mueller, P. S., Montori, V. M., Bassler, D., Koenig, B. A., & Guyatt, G. H.
Affiliations: Mayo Clinic (US)
From Mayo Clinic College of Medicine, Rochester, Minnesota; University Children's Hospital, Tuebingen, Germany; and McMaster University, Hamilton, Ontario, Canada.
ORCID: Mueller, Paul S.
Bassler, Dirk
Koenig, Barbara A.
Guyatt, Gordon H.
Venue: Annals of Internal Medicine
Publisher: American College of Physicians
Published: 2007-06-19
Volume: 146
Issue: 12
Pages: 878-881
ISSN: 0003-4819 (ISSN-L)
1539-3704
DOI: 10.7326/0003-4819-146-12-200706190-00009
OpenAlex: W2148390494
Cited by: 202
References: 20
Citations by year: 2026: 6 · 2025: 3 · 2024: 30 · 2023: 10 · 2022: 10 · 2021: 5 · 2020: 13 · 2019: 8 · 2018: 2 · 2017: 9 · 2016: 12 · 2015: 15 · 2014: 5 · 2013: 10 · 2012: 13
Type: journal article
Language: en
Open access: closed
Licence: www.acpjournals.org/journal/aim/text-and-data-mining (tdm)
Locations: Annals of Internal Medicine (publishedVersion)
PubMed (publishedVersion)
DigitalGeorgetown (Georgetown University Library) (submittedVersion)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Health Sciences › Nursing › Issues, ethics and legal aspects › Biomedical Ethics and Regulation
Keywords: early trial termination, randomized controlled trials, trial ethics, scientific validity, risk-benefit ratio, social values
MeSH terms: Humans, Informed Consent, Social Values, Reproducibility of Results, Bias, Randomized Controlled Trials as Topic, Risk Assessment, Ethics Committees, Research

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Ethical issues in stopping randomized trials early because of apparent benefit.

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